New gene variants identified that cause hypertension in pregnant women

A new international study – jointly funded by an NIHR and Medical Research Council (MRC) partnership and supported by the NIHR Cambridge and Oxford BRC – has found a unique pair of gene variants that cause sudden onset high blood pressure in pregnant women.

Led by researchers from the Queen Mary University of London (QMUL) and St Bartholomew’s Hospital, the results have now been published in the journal Nature Genetics.

Hypertension (high blood pressure) affects 30% of adults. Most cases are caused by a combination of inherited and acquired factors that require long-term treatment to prevent the complications of stroke and heart attacks.

For one in ten people with hypertension, a specific cause can be found and removed. The most common cause is a tiny benign nodule in one of the adrenals. These are glands near the kidneys that produce steroid hormones.

The hormone aldosterone stimulates the kidneys to retain salt and hence increase blood pressure. As a result, the condition known as primary aldosteronism typically leads to a type of hypertension which is resistant to conventional drugs, and is linked to an increased risk of stroke and heart attacks compared to other patients with hypertension.

The research team have found a number of gene variants which cause the production of high levels of aldosterone from small adrenal nodules. Their latest study involves a discovery of a new type of primary aldosteronism caused by the coincidence of a unique pair of new variants which always occur together. The patients are predominantly women, who present with sudden onset of high blood pressure and low blood potassium in the early months of a pregnancy.

In partnership with Professor Christina Zennaro, Inserm Research Director at the Paris Cardiovascular Research Center, and colleagues in Paris, it emerged the new variants switch on a receptor molecule in the adrenal cells which recognises the pregnancy hormone Human Chorionic Gonadotropin (HCG), the same as is measured in routine pregnancy testing – and that the receptor molecule triggers a surge of aldosterone production.

Professor Morris Brown, Professor of Endocrine Hypertension at Queen Mary University of London said: “What was particularly satisfying is that recognition of the cause of hypertension in these women enabled them to complete a successful pregnancy, and that afterwards they were completely cured of hypertension by a procedure to remove the adrenal nodule, and were able to stop all their drugs.”

The study was jointly funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership, and also received funding from the British Heart Foundation and Barts Charity.

Adapted from NIHR article